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A1-G Surg Note Stomach > Gastrointestinal Stromal Tumors > Flashcards

Gastrointestinal Stromal Tumors Flashcards

1
Q

What is the most common sarcoma of the gastrointestinal (GI) tract?

A

Gastrointestinal stromal tumor (GIST).

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2
Q

What type of cells are GISTs derived from?

A

Mesenchymal cells known as interstitial cells of Cajal.

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3
Q

Where do GISTs most commonly present in the GI tract?

A

The stomach, followed by the small bowel, rectum, and colon.

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4
Q

What mutation is most commonly associated with GISTs?

A

Gain of function mutation in the KIT proto-oncogene, found in about 75% of GISTs.

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5
Q

What percentage of KIT-wild type (WT) tumors have mutations in platelet-derived growth factor receptor (PDGFR) α?

A

Approximately 80% of KIT-WT tumors.

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6
Q

What other mutation has been reported in KIT-WT GISTs, and what is its prevalence?

A

BRAF mutations, found in 13% of KIT-WT tumors.

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7
Q

Which familial syndromes are associated with KIT-WT GISTs?

A

Neurofibromatosis type 1 (NF1) and mutations in succinate dehydrogenase (SDH)

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8
Q

What is the role of Imatinib mesylate (Gleevec) in the treatment of GIST?

A

It is a TKI that targets ABL, BCR-ABL, KIT, and PDGFR, used in both metastatic and adjuvant settings for GIST management.

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9
Q

What is the benefit of neoadjuvant Imatinib therapy in GIST?

A

It may improve resectability of locally advanced tumors and allow for organ-preserving surgery in anatomically challenging locations.

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10
Q

What factors are used to estimate the risk of recurrence in GIST patients?

A

Tumor size
mitotic index
organ site
specific mutations in KIT.

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11
Q

What is the typical age and gender distribution for GIST?

A

in adults, median presenting age of 60 years and a slight male predominance

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12
Q

Where are GISTs most commonly found within the GI tract?

A

The majority are found in the stomach (> 50%), followed by the small bowel (25%–35%).

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13
Q

Which sections of the small bowel are most commonly affected by GISTs?

A

Most small bowel GISTs are found in the ileum and jejunum, with only 5% in the duodenum

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14
Q

How are GISTs commonly discovered?

A

Often incidentally during endoscopy, imaging, or unrelated surgeries.

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15
Q

What symptoms may present with larger GISTs?

A

Pain, fullness, early satiety, nausea, vomiting, weight loss, or a noticeable mass

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16
Q

Why might approximately one-quarter of GIST patients present with GI bleeding?

A

Due to erosion and ulceration of the underlying mucosa.

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17
Q

What is a rare but serious prognostic factor related to bleeding in GIST?

A

Tumor rupture into the peritoneal cavity, which may lead to life-threatening hemorrhage

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18
Q

Where does GIST typically metastasize?

A

Metastasis usually involves the liver or peritoneal cavity.

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19
Q

How common is lymph node involvement in adult GIST

A

It is rare, occurring in less than 5% of patients.

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20
Q

What characterizes pediatric GIST compared to adult GIST?

A

Pediatric GIST often involves SDH deficiency, is indolent, has female predominance, multifocal disease, frequent lymph node metastasis, and is universally resistant to imatinib.

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21
Q

What are familial GISTs associated with?

A

Germline mutations in KIT or PDGFRα, typically presenting as multifocal and indolent tumors

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22
Q

What are Carney’s triad and Carney-Stratakis syndrome?

A

Carney’s triad includes GIST, paraganglioma, and pulmonary chondroma

Carney-Stratakis syndrome involves GIST and paraganglioma

both associated with SDH mutations

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23
Q

Which other tumors might patients with NF1 mutations develop along with GIST?

A

gliomas, malignant peripheral nerve sheath tumors, and neurofibromas

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24
Q

What is the imaging modality of choice for the initial evaluation of a GIST?

A

Cross-sectional imaging with a computed tomography (CT) scan of the abdomen and pelvis with IV and oral contrast

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25
Q

What are the typical CT scan features of a GIST?

A

An enhancing mass arising in the wall of the stomach or small intestine

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26
Q

How can GIST tumors be grossly categorized?

A

As exophytic, endophytic, or mixed/dumbbell-shaped.

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27
Q

Why might smaller GIST tumors not be visible on a CT scan?

A

They may be obscured depending on the level of bowel or stomach distention and whether oral contrast was administered.

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28
Q

What large mass might be misinterpreted as a primary liver tumor on a CT scan?

A

A large hypervascular mass arising from the lesser curvature of the stomach.

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29
Q

When is MRI particularly useful in evaluating GIST?

A

For further delineating anatomy in periampullary and rectal tumors.

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30
Q

Is PET/CT necessary for the initial assessment of GIST?

A

No, but
it may be considered for detecting occult metastatic disease and assessing tumor response to TKIs.

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31
Q

What role does PET/CT have for NF1 patients in GIST evaluation?

A

It may help distinguish neurofibromas from GIST tumors

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32
Q

What is the next step in evaluation if a CT scan shows features suggestive of GIST?

A

Endoscopic evaluation, including endoscopic ultrasound (EUS) and fine-needle aspirate (FNA).

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33
Q

Why should percutaneous biopsies be avoided for small bowel GISTs?

A

Due to the risk of peritoneal dissemination.

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34
Q

What is the gold standard for confirming a GIST diagnosis?

A

Tissue analysis to rule out other potential tumors and confirm the presence of GIST.

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35
Q

What cell type is typically seen on pathology for GIST, and which marker is used for confirmation?

A

Spindle cells that stain positive for CD117 (KIT) on immunohistochemistry

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36
Q

Why is tissue analysis important beyond confirming GIST?

A

To detect additional genetic mutations (e.g., PDGFRα, BRAF, SDH, NF1) and guide targeted therapy.

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37
Q

For which GIST tumor locations is tissue diagnosis particularly necessary?

A

Tumors at the gastroesophageal junction (GEJ), periampullary duodenum, or rectum that may require a potentially morbid operation.

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38
Q

see

A
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39
Q

What are the three clinicopathologic parameters that independently predict recurrence risk after complete resection of primary GIST?

A

Tumor size, mitotic rate, and tumor site

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40
Q

What tumor characteristics are considered poor prognostic indicators in GIST?

A

Tumor size greater than 5 cm
mitotic rate over 5/50 high-powered field (HPF)
nongastric tumor site.

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41
Q

How can identifying specific mutations (e.g., KIT, PDGFR, SDH) in GIST be beneficial?

A

It provides information on responsiveness to targeted therapy and progression-free survival (PFS) after resection.

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42
Q

What is the most common KIT mutation, and where does it commonly occur in GIST?

A

Exon 11 mutation, occurring in 65% of all GISTs.

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43
Q

What is the significance of deletions in codons 557 and 558 of KIT exon 11?

A

Tumors with these deletions are more likely to metastasize or recur compared to other mutation types.

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44
Q

What did the ACOSOG Z9001 study reveal about KIT exon 11 deletions and adjuvant imatinib?

A

Patients with KIT exon 11 deletions showed significant improvement in RFS with 1 year of adjuvant imatinib.

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45
Q

Which KIT mutation is associated with nongastric GIST and has more aggressive biology?

A

KIT exon 9 mutation, found in about 10% of GISTs.

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46
Q

What is the recommended imatinib dose for patients with KIT exon 9 mutations in metastatic unresectable GIST?

A

A higher dose of 800 mg daily, as opposed to the standard 400 mg.

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47
Q

What percentage of GISTs have PDGFRα mutations, and where are they typically located?

A

About 10%, almost always in the stomach.

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48
Q

What is the significance of the PDGFRα exon 18 (D842V) mutation in GIST?

A

It confers resistance to imatinib but responds to avapritinib therapy.

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49
Q

Which FDA-approved drug is used as first-line therapy for GIST patients with the PDGFRα exon 18 (D842V) mutation?

A

Avapritinib.

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50
Q

According to the National Comprehensive Cancer Network (NCCN), when is resection indicated for GISTs

A

For all GISTs greater than 2 cm in size in patients who are suitable surgical candidates

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51
Q

How are GISTs smaller than 2 cm managed if they are asymptomatic and indolent?

A

They can be observed with surveillance imaging

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52
Q

When might surgical resection be considered for patients with locally advanced or low volume metastatic GIST?

A

In selected cases, potentially along with neoadjuvant therapy

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53
Q

What is the guideline for imatinib therapy in patients undergoing surgery?

A

Imatinib can be stopped right before surgery and restarted once the patient tolerates oral medications

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54
Q

What is the guideline for other tyrosine kinase inhibitors (TKIs) in the perioperative period for GIST surgery?

A

Other TKIs should be stopped at least 1 week before surgery and restarted based on clinical judgment and recovery.

55
Q

What areas should be examined upon entry into the abdominal cavity during GIST surgery?

A

The peritoneum, omentum, and liver should be checked for metastatic disease

56
Q

Which gastric tumors are immediately visible upon entry?

A

Exophytic anterior and greater curvature gastric tumors.

57
Q

How are posterior gastric tumors accessed during GIST surgery?

A

By retracting the left lobe of the liver to the right and entering the lesser sac through the greater omentum or gastrocolic ligament.

58
Q

What method helps localize small intramural or endophytic gastric tumors during surgery?

A

Intraoperative endoscopy using a gastroscope.

59
Q

What maneuver is required for accessing duodenal tumors beyond the first portion?

A

Extensive Kocher maneuver and potentially mobilizing the ligament of Treitz

60
Q

How are ileal and jejunal GISTs identified during surgery?

A

By carefully running the small bowel from the ligament of Treitz to the terminal ileum

61
Q

Why must GIST tumors be handled carefully during surgery

A

They are friable and may rupture, leading to a high risk of peritoneal recurrence

62
Q

What is a key consideration regarding blood vessels in GIST surgery?

A

GISTs often have large arterial and venous collaterals, so care is needed to prevent significant blood loss.

63
Q

Do GISTs typically require wide resection margins or lymphadenectomy like gastric adenocarcinoma?

A

No, GIST resection does not require wide margins or lymphadenectomy because they do not usually spread via lymphatics.

64
Q

What is the goal of GIST surgery in terms of resection margins?

A

To achieve an R0 resection with microscopically negative margins.

65
Q

What did the American College of Surgeons Oncology Group Z900 and Z9001 trials reveal about R1 resection in GIST?

A

No difference in recurrence-free survival (RFS) between R1 resection and R0 resection, regardless of imatinib treatment

66
Q

What circumferential margin is recommended to achieve an R0 resection in GIST surgery?

A

A gross circumferential margin of 1 cm

67
Q

What surgical approach is suitable for exophytic gastric GISTs with a narrow stalk on the greater curvature or fundus?

A

Wedge partial gastrectomy using surgical staples without compromising the lumen

68
Q

Which areas of the stomach require direct visualization to safely resect GISTs without luminal narrowing

A

The antrum, incisura, lesser curvature, and gastroesophageal junction (GEJ)

69
Q

What technique is used for excising gastric GISTs with a small negative margin?

A

Excision under direct visualization with a small margin (usually 1 cm) using cautery

70
Q

When should neoadjuvant imatinib be considered for a GIST located at the GEJ?

A

For tumor downsizing before resection

71
Q

What surgical approach is typically preferred for GISTs on the posterior aspect of the GEJ?

A

Open surgery, although minimally invasive options are possible

72
Q

During open surgery for a GEJ GIST, what is the purpose of placing a bougie in the esophagus?

A

To avoid narrowing the GEJ during reconstruction

73
Q

Describe the minimally invasive approach to excise a posterior GEJ GIST.

A

An anterior gastrotomy is created for visualization, excising the tumor with a small margin, closing the posterior gastrotomy in the direction of the widest lumen, placing a bougie, and closing the anterior gastrotomy.

74
Q

What precaution is necessary when resecting GISTs from the lesser curvature of the stomach?

A

Careful dissection to preserve vagal nerve integrity.

75
Q

What procedure should be performed if the vagal trunks cannot be preserved during lesser curvature GIST resection?

A

Pyloroplasty or pyloromyotomy.

76
Q

When might total gastrectomy or esophagogastrectomy be necessary for GIST treatment?

A

For sizable tumors involving a large area of the lesser curvature or the gastroesophageal junction (GEJ), respectively.

77
Q

What might necessitate en bloc resection in GIST surgery?

A

Massive tumors adherent to nearby organs such as the spleen, distal pancreas, or colon

78
Q

What is the preferred approach if organ-preserving resection is desired for a large GIST

A

Neoadjuvant imatinib to achieve tumor downsizing and devascularization preoperatively

79
Q

What is the second most common site of GISTs after the stomach?

A

The small bowel.

80
Q

How are jejunal and ileal GISTs typically resected?

A

With open or minimally invasive techniques, with small bowel anastomosis performed intracorporeally or extracorporeally

81
Q

What makes management of duodenal GISTs complex?

A

Their proximity to the pancreas and bile duct.

82
Q

When should neoadjuvant imatinib be considered for a duodenal GIST?

A

When a pancreatoduodenectomy might be necessary for complete resection

83
Q

What technique facilitates ampulla localization in cases of duodenal GIST near the ampulla?

A

Cholecystectomy with cystic duct cannulation using a 4Fr Fogarty catheter

84
Q

How are small GISTs of the duodenum managed if they do not involve the periampullary region?

A

They can be resected without requiring pancreatectomy.

85
Q

What surgical procedure is often required for periampullary GISTs involving the medial duodenal wall?

A

Pancreatoduodenectomy, even after neoadjuvant imatinib

86
Q

How can small GISTs of the lateral wall of the duodenum’s second portion be managed?

A

They can be excised, with the defect closed by suture duodenorrhaphy or a Roux-en-Y duodenojejunostomy.

87
Q

How are tumors in the third or fourth portion of the duodenum managed?

A

With segmental duodenectomy followed by primary duodenojejunostomy.

88
Q

How common are rectal GISTs compared to colonic GISTs?

A

Rectal GISTs are much more common than colonic GISTs

89
Q

What is the role of neoadjuvant imatinib in the treatment of large rectal GISTs?

A

It aids in tumor downsizing and sphincter preservation

90
Q

How are small GISTs of the lower rectum typically excised?

A

Transanally, potentially using transanal endoscopic mucosal surgery

91
Q

What is the current NCCN guideline for gastric GISTs under 2 cm with no concerning risk factors?

A

Active surveillance is recommended.

92
Q

Under what conditions is endoscopic management of GIST considered feasible and safe?

A

For upper GI tract GISTs < 5 cm, after excluding high-risk features like high mitotic rate, enlarged lymph nodes, irregular margins, internal heterogeneity, and cystic spaces on EUS

93
Q

Name three endoscopic procedures used for managing small GISTs

A

Endoscopic band ligation (EBL)
endoscopic submucosal dissection (ESD)
endoscopic full thickness resection (EFTR).

94
Q

What are two advanced techniques combining laparoscopic and endoscopic approaches for GIST removal?

A

Laparoscopic endoscopic cooperative surgery (LECS) and nonexposed endoscopic wall-inversion surgery (NEWS).

95
Q

What types of GISTs based on gastric wall location are suitable for endoscopic enucleation?

A

Types 1 and 2.

96
Q

Which endoscopic techniques are appropriate for types 1 and 2 GISTs?

A

Endoscopic band ligation (EBL), endoscopic submucosal dissection (ESD), endoscopic mucosal dissection (EMD), endoscopic submucosal tunnel dissection (ESTD), and submucosal tunneling endoscopic resection (STER).

97
Q

For which GIST types are EFTR, LECS, NEWS, and CLEAN-NET recommended?

A

Types 3 and 4, which are not amenable to endoscopic enucleation

98
Q

What is CLEAN-NET in the context of GIST management?

A

A combination of laparoscopic and endoscopic approaches to neoplasia with a nonexposed technique.

99
Q

What characterizes a Type I GIST in the gastric wall?

A

It has a very narrow connection with the proper muscle layer and protrudes into the luminal side like a polyp

100
Q

How does a Type II GIST differ from Type I regarding its connection to the muscle layer?

A

Type II has a wider connection with the proper muscle layer and protrudes into the luminal side at an obtuse angle.

101
Q

Where is a Type III GIST located within the gastric wall?

A

It is situated in the middle of the gastric wall.

102
Q

In which direction does a Type IV GIST primarily protrude?

A

It protrudes mainly into the serosal side of the gastric wall.

103
Q

What are the four layers of the gastric wall involved in GIST classification?

A

1: Mucosa
2: Submucosa
3: Circular layer of proper muscle
4: Longitudinal layer of proper muscle

104
Q

When should neoadjuvant imatinib treatment be considered for nonmetastatic GISTs?

A

For tumors that are locally advanced, require multivisceral resections, or are in anatomically challenging locations where downsizing may reduce surgical morbidity

105
Q

Which therapy should be used for patients with the D842V mutation of exon 18 in the PDGFRα gene?

A

Avapritinib, due to imatinib resistance

106
Q

When should a follow-up contrast-enhanced CT scan be obtained after starting neoadjuvant imatinib?

A

Within 6 to 8 weeks.

107
Q

How often is surveillance imaging typically performed during neoadjuvant imatinib therapy?

A

Every 3 months.

108
Q

After how many months of neoadjuvant imatinib is further tumor downsizing unlikely?

A

Beyond 6 months

109
Q

How does neoadjuvant imatinib differ from cytotoxic chemotherapy regarding perioperative management?

A

It can be continued up until surgery without affecting wound healing or causing immunosuppression

110
Q

When can imatinib therapy be resumed postoperatively?

A

When the patient is eating normally and has regained bowel function.

111
Q

What is the guideline for stopping avapritinib or other TKIs before surgery?

A

They should be stopped at least 1 week prior and restarted based on clinical recovery.

112
Q

How did the long-term follow-up of the Z9001 study impact understanding of imatinib’s effects?

A

It showed that while imatinib controls residual disease, it does not eradicate it, as RFS curves converged after 74 months of follow-up

113
Q

Which mutation was primarily associated with improved RFS in the Z9001 study?

A

Exon 11 deletion in the KIT gene

114
Q

What did the SSG XVIII study compare, and what were its findings?

A

It compared 1 year vs. 3 years of adjuvant imatinib, finding that 3 years improved 5-year RFS (66% vs. 48%) and slightly improved overall survival (92% vs. 82%)

115
Q

What was the focus of the PERSIST-5 trial, and what were its results?

A

It examined 5 years of adjuvant imatinib in high-risk GIST patients, showing effectiveness in preventing recurrence for those with sensitive KIT mutations

116
Q

Which patients were included in the PERSIST-5 study criteria for high recurrence risk?

A

GISTs of any site ≥ 2 cm with ≥ 5 mitoses/50 HPF or any nongastric GIST ≥ 5 cm.

117
Q

What is the primary benefit of extended adjuvant imatinib treatment in high-risk GIST patients?

A

It significantly reduces the risk of recurrence, especially in patients with sensitive KIT mutations.

118
Q

What is the typical median time to disease progression with imatinib alone in GIST patients

A

Approximately 24 months.

119
Q

What commonly causes disease progression in GIST patients on imatinib?

A

The development of secondary mutations in KIT, often in exons 13, 14, or 17.

120
Q

How is imatinib resistance detected during radiographic surveillance?

A

By the appearance of enhancing nodules within a previously nonviable, necrotic tumor.

121
Q

How frequently should imaging be performed for patients with recurrent or metastatic GIST on TKI therapy?

A

Every 3 months

122
Q

When can surgical resection be considered in GIST patients with tumor resistance?

A

In carefully selected patients with limited disease burden, especially those with partial response to TKI therapy.

123
Q

Which patients benefit most from surgery after TKI therapy in GIST management?

A

Those with partially responsive tumors, as opposed to those with rapid or multifocal resistance patterns

124
Q

What is the recommended approach for hepatic GIST metastases?

A

Resection or ablation aimed at clearing all detectable tumor sites, with preservation of liver parenchyma

125
Q

What is the management strategy for peritoneal GIST metastases?

A

Surgical resection, potentially requiring removal of adjacent organs

126
Q

What is the postoperative management for GIST patients after resection of hepatic or peritoneal metastases?

A

Indefinite adjuvant TKI therapy or until recurrence develops

127
Q

What is the partial response of imatinib-resistant GIST tumors to second-line TKI therapy?

A

Second-line TKIs, like sunitinib, can improve progression-free survival (PFS) from 6 weeks to 27 weeks.

128
Q

How does third-line TKI therapy with regorafenib compare to second-line treatment?

A

Regorafenib improves PFS from 0.9 to 4.8 months, showing diminishing returns with each line of therapy.

129
Q

Adjuvant imatinib should be used for at least ?

A

3 years in patients at high risk for disease recurrence predicted by individualized nomograms.

130
Q

Schematic approach to patients with gastrointestinal stromal tumor (GIST).

A

see

131
Q

primary tumors treated with adjuvant imatinib, tumor density should be assessed by CT at

A

4 weeks to document response to therapy.

132
Q

If GIST nomogram predicts a high or intermediate risk of recurrence

A

adjuvant imatinib should be continued for at least 3 years, possibly chronically

133
Q

Surveillance after resection of GIST should include

A

CT of abdomen and pelvis every 3 to 6 months for
3 to 5 years and then annually

A1-G Surg Note Stomach (11 decks)

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